Modulation of the ethanol-like discriminative stimulus effects of diazepam and phencyclidine by L-type voltage-gated calcium-channel ligands in rats |
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Authors: | K. Green-Jordan K. A. Grant |
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Affiliation: | (1) Department of Psychology, Boston University, 64 Cummington Street, Boston, MA 02215-2407, USA, US;(2) Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1083, USA e-mail: kagrant@isnet.wfu.edu, Tel.: +1-336-716-8651, Fax: +1-336-716-8501, US |
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Abstract: | Rationale: Administration of voltage-gated calcium-channel (VGCC) modulators with ethanol can result in enhancement or attenuation of some behavioral effects of ethanol, including its discriminative stimulus effects. Objectives: The present study used a drug- discrimination paradigm to characterize modulation of the ethanol-like discriminative stimulus effects of a γ-amino-butyric acid (GABA)A and N-methyl-d-aspartate (NMDA) ligand by administration of VGCC ligands. Methods: Two groups of adult male Long-Evans rats were trained to discriminate either 1.0 g/kg ethanol (n=8) or 2.0 g/kg ethanol (n=9) from water under a fixed-ratio (FR) 20 schedule of food presentation. Following training, ethanol substitution tests were conducted with cumulative doses of the GABAA-positive modulator diazepam (0.3–10 mg/kg, i.p.) (DZP) and the uncompetitive NMDA antagonist phencyclidine (0.3–5.6 mg/kg, i.p.) (PCP). Next, a single dose of the VGCC antagonist nimodipine, nifedipine, isradipine, or the VGCC agonist (–)-BAY k 8644 (0.3 mg/kg, i.p.) was administered prior to a cumulative DZP or PCP dose–response determination. Results: None of the VGCC modulators produced robust or consistent alterations in the ethanol-like discriminative stimulus effects of DZP in animals trained with either 1.0 g/kg or 2.0 g/kg ethanol. However, the ethanol-like discriminative stimulus effects of PCP were significantly enhanced in the presence of the VGCC antagonists and attenuated in the presence of the agonist in animals trained with 2.0 g/kg ethanol. Conclusions: Overall, these data show that VGCC modulation is not a robust component of ethanol-like discriminative stimulus effects of DZP in animals trained with 1.0 g/kg or 2.0 g/kg ethanol. However, the ethanol-like effects of PCP, particularly at higher training doses, appear to be modulated by dihydropyridine-sensitive VGCCs. Received: 26 August 1999 / Final version: 22 October 1999 |
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Keywords: | Ethanol Drug discrimination Voltage-gated calcium channel NMDA GABAA |
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